Cell adhesion, migration, and morphogenesis are crucial events in craniofacial development, and errors in them can result in congenital anomalies. Related biological processes appear to be important for normal adult wound repair. We are characterizing molecules that mediate or regulate these processes by structural and functional analyses. The extracellular glycoprotein fibronectin is important for both morphogenesis and epithelial wound healing, e.g. for migration of craniofacial neural crest cells. Regions of fibronectin essential for cell adhesion and migration were characterized in detail by site-directed mutagenesis, homology scanning, and monoclonal antibody approaches. Collaborative molecular structural studies are in progress to characterize further the requirements for fibronectin function. This information should facilitate the rational design of novel bioadhesives and inhibitors. Vitronectin is another major extracellular adhesion molecule. Analysis of mRNA expression was striking in the spinal cord floor plate of mouse embryos. This structure is important for neuronal development, and vitronectin may be a novel effector molecule. Fibronectin, vitronectin, and certain other adhesion molecules share the Arg-Gly- Asp sequence, and treatment of embryos with inhibitory peptides containing this sequence was found to induce specific tissue-specific cell surface morphological responses. Adhesion, migration, and morphogenesis are regulated by a variety of factors, including transcription factors. We are characterizing the role of a putative transcription factor, the zinc-finger protein Slug, in triggering the first steps of epithelial-mesenchymal transition, which is a process essential for cranial neural crest cell migration. We have also identified a novel gene associated with this process. These studies should provide a molecular understanding of the regulation of these important but complex morphogenetic processes.